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Obestatin Plays Beneficial Role in Cardiomyocyte Injury Induced by Ischemia-Reperfusion In Vivo and In Vitro

Qin Zhang, Xin-wei Dong, Jia-ying Xia, Ke-ying Xu, Zhe-rong Xu

(Department of Geriatrics, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China (mainland))

Med Sci Monit 2017; 23:2127-2136

DOI: 10.12659/MSM.901361

Published: 2017-05-04


BACKGROUND: Obestatin, primarily recognized as a peptide within the gastrointestinal system, has been shown to benefit the cardiovascular system. We designed this experiment to study the protective role and underlying mechanism of obestatin against ischemia-reperfusion(I/R) injury in myocardial cells.
MATERIAL AND METHODS: In an In vivo experiment, LAD was ligated for 0.5 h and then opened for reperfusion with obestatin for 24 h. Then, the infarction area was shown with TTC staining, and inflammation factors in serum were analyzed by qRT-PCR. In primary cultured cardiomyocytes, we measured the level of LDH, MDA, GSH, and SOD. Finally, we assessed cells apoptosis using flow cytometry and detected the concentrations of caspase-3, Bax, and Bcl-2 using Western blot analysis.
RESULTS: TTC staining showed that in the 3 obestatin groups, the infarct area became smaller with the increase of obestatin concentration. Obestatin also inhibited LDH expression in rat serum and decreased mRNA levels of TNF-α, IL-6, ICAM-1, and iNOS in rat cardiomyocytes after reperfusion. In primary cultured cardiomyocytes, obestatin decreased LDH content and increased GSH level after I/R injury. Obestatin was also found to antagonize the apoptosis of cardiomyocytes in a dose-dependent manner. Western blot analysis showed that obestatin downregulated the expression of caspase-3 and Bax and upregulated the expression of Bcl-2.
CONCLUSIONS: Obestatin can protect cardiomyocyte from I/R-induced injury in vitro and in vivo. This beneficial effect is closely related with its properties of anti-inflammation, anti-cytotoxicity, and anti-apoptosis. The protective effect of obestatin might be associated with activation of Bcl-2 and inhibition of caspase-3 and Bax.

Keywords: Ghrelin, Myocardial Infarction, Myocytes, Cardiac, Reperfusion Injury



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